STRYCHNINE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Estricnina
2) Strychnina
3) Strychnidin-10-one
4) Molecular Formula: C21H22N2O2
5) CAS 57-24-9

1) Azotato de Estricnina
2) Nitrato de Estricnina
3) Strychninae Nitras
4) Strychninum Nitricum
5) Molecular Formula: C21H23N3O5
6) CAS 66-32-0

1) Molecular Formula: C21H25N2O6P
2) CAS 509-42-2

1) Strychninae sulphas
2) Strychninum sulfuricum
3) Sulfato de Estricnina
4) Molecular Formula: (C21H22N2O2)2.H2S04.5H2O
5) CAS 60-41-3 (anhydrous)
6) CAS 60491-10-3 (pentahydrate)

1) STRYCHNINE AND SALTS
2) STRYCNIDIN-10-ONE, AND SALTS

1.2.1) MOLECULAR FORMULA
1) C21-H22-N2-O2

Available Forms Sources

1) Purified strychnine in bulk form can be obtained from chemical supply companies.
2) Pesticide and rodenticide preparations available to the public contain 0.3% to 0.5% strychnine where those used by licensed exterminators may contain up to 5% strychnine.
3) Trade names of common animal poisons which contain strychnine include:

El Roy Mouse Bait        Mole-Nots/Mole O Nots
Gopher Bait/Mix/Tabs     Mouse Maize/Seeds
Gopher Death             Mologen Mouse Lure
Gopher Getter            Orco Gopher Bait
Gopher Go                Pied Piper Kwik-Kill
Hot Spring Buttons       Pigeon-9
Kilmice                  Rad-Seed
Mice Doom Pellets        Senco Poison Oat Kernels
Mo-Go                    Sparrow Cracks
                         Sweeney's Poison Wheat

1) ADULTERATED/CONTAMINATED STREET DRUGS

a) Strychnine may be added as an adulterant to street drugs such as amphetamines, cocaine, and heroin to "cut" them (increase their volume).
b) Strychnine has been misrepresented as cocaine and sold as such on the streets (Boyd et al, 1983; Decker et al, 1982; O'Callaghan et al, 1982).
c) The following street drugs may contain strychnine: "back breakers", "homicide", "red rock opium", "red rum", and "red stuff" and "spike" (Radosavljevic et al, 2006).

2) LABORATORY/RESEARCH USE

a) Purified strychnine alkaloid and strychnine salts are used in pharmacological research related to drug-induced seizures and the function and location of glycine and its receptors.

3) PESTICIDES/RODENTICIDES

a) Strychnine had been used primarily as a pesticide and rodenticide. Bait impregnated with strychnine was used to poison birds (eg, pigeons), gophers, mice, moles, rats, rabbits, porcupines, and wild carnivores (eg, coyotes, foxes, wolves).
b) In many countries, strychnine is no longer approved for use to control predators (Radosavljevic et al, 2006), and sales of strychnine are prohibited (Parker et al, 2011).

4) THERAPEUTIC PREPARATIONS

a) Strychnine is restricted to the treatment of nonketotic hyperglycinemia (an inborn error of glycine metabolism) (Radosavljevic et al, 2006).
b) In the past, preparations were used as bitters, cathartics, tonics, and circulatory stimulants, but are now considered ineffective and dangerous for such uses (Baselt, 2000). However, strychnine may still be found in some multi-ingredient products in Austria, France and Italy (Radosavljevic et al, 2006).

5) STRYCHNINE PILLS

a) Pills containing strychnine were formerly used as human and veterinary analeptics, analgesics, aphrodisiacs, cathartics, circulatory stimulants, and tonics.
b) Strychnine was often used in combination with acetophenetidin, aloin, aspirin, arsenic, belladonna, caffeine, camphor, capsicum, cascara, gelsemium, ipecac, iron, phenolphthalein, podophyllin, quinine, thioridazine, yohimbine.
c) Although no longer marketed, strychnine-containing pills may still be available in home medicine cabinets. These preparations are now considered ineffective as well as dangerous.
d) Accidental or intentional ingestion of Easton's tablets (Formula A = iron phosphate 200 mg, quinine sulfate 50 mg strychnine hydrochloride 1 mg; Formula F = one-half strength Formula A) was formerly a common cause of strychnine poisoning with cases being reported as recently as 1971 (Jackson et al, 1971).
e) Strychiomel tablets each containing 1.5 mg strychnine, 10 mg thioridazine and 2.5 mg yohimbine, have recently been studied for the treatment of impotence (Savion et al, 1987).
f) Strychnine (0.1 mg/kg orally) has also been studied in the treatment of sleep apnea (Remmers et al, 1980).
g) Strychnine has also been used in the treatment of encephalopathy, due to nonketotic hyperglycinemia (Chien et al, 1978; Haan et al, 1986).

6) INTRAVENOUS STRYCHNINE

a) Strychnine has been used intravenously for the treatment of glycine encephalopathy (nonketotic hyperglycinemia) (Sankarin et al, 1982).
b) Strychnine has been used as an agent of criminal homicide, execution and suicide.

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Used mainly as a pesticide and a rodenticide. Also, used in some laboratories as a research tool to study glycine receptors.
B) EPIDEMIOLOGY: Exposures to strychnine are becoming increasingly rare, though deaths still occur. It can be found in some Chinese herbal medicines, in the slang nut from Cambodia, and also as a street drug adulterant.
C) TOXICOLOGY: Competitively inhibits glycine binding to the alpha-subunit of the glycine-regulated chloride channel in the spinal cord. Glycine acts as an inhibitory neurotransmitter in the spinal cord. It opens chloride channels allowing the influx of chloride into cells leading to hyperpolarization and inhibition. Thus, inhibition of glycine binding to this receptor causes excitation of the muscle directly stimulated by the spinal cord.
D) WITH POISONING/EXPOSURE

1) OVERDOSE: GASTROINTESTINAL: Nausea and vomiting occur uncommonly. CNS EFFECTS: Bilateral horizontal nystagmus and blurred vision have been reported. Muscle tightness/cramps, agitation, and heightened sensitivity to stimulation may precede severe neurologic toxicity. Neurologic symptoms occur quickly (within 15 to 30 minutes) and include agitation, severe hypertonicity of muscles, opisthotonos, and painful muscle spasms. Trismus and risus sardonicus are also reported. The patient usually remains alert throughout this convulsive activity. Auditory, tactile, or visual stimulation may trigger a violent motor response. OTHER: Tachycardia, hypertension, tachypnea, and hyperthermia are seen commonly secondary to neuromuscular hyperactivity. RESPIRATORY FAILURE: Patients may also present with bradycardia and hypotension in cases of respiratory failure/arrest. Involvement of the respiratory muscles leads to diaphragm paralysis resulting in hypoxia and hypercarbia. RENAL FAILURE: Acute renal failure can occur secondary to myoglobinuria, rhabdomyolysis, and crystalluria. METABOLIC: Additionally, a lactic acidosis can develop as a result of the neuromuscular hyperactivity and powerful muscle contractions. Respiratory acidosis is a terminal sign owing to diaphragmatic paralysis. FATALITIES: Early death are usually the result of respiratory failure. Late death are generally secondary to either anoxic brain injury or multiorgan system failure secondary to hyperthermia.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Tachycardia, hypertension, tachypnea, and hyperthermia may be seen.
2) In severe cases, respiratory paralysis (apnea) with bradycardia, hypotension, and cardiac arrest may occur.

0.2.4)

A) WITH POISONING/EXPOSURE

1) EYES: Bilateral horizontal pendular nystagmus and blurred vision have been reported.

0.2.11)

A) Both metabolic (lactic) and respiratory acidosis may be noted.

0.2.20)

A) Pre-implantation mortality and stillbirth were observed in rats.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Neurologic symptoms (ie, agitation, severe hypotonicity of muscles) are likely to occur within 15 to 30 minutes. For muscle spasm, administer IV benzodiazepines. DIAZEPAM DOSE: ADULT: Initial: 5 to 10 mg which may be repeated every 5 to 10 minutes as needed; PEDIATRIC: 0.25 to 0.4 mg/kg/dose up to 10 mg/dose). If muscle spasms and/or convulsions cannot be controlled or recur, administer phenobarbital or propofol. Avoid unnecessary stimulation (ie, visual, tactile, or auditory) as these may precipitate spasms and/or convulsions. Patients who are treated aggressively over the first 6 to 12 hours and can avoid anoxia, severe acidosis, hyperthermia or respiratory failure, will recover.

B) MANAGEMENT OF SEVERE TOXICITY

1) Early aggressive sedation, neuromuscular paralysis and airway management should prevent death in severely toxic cases. Spasms and convulsions refractory to diazepam and phenobarbital or respiratory failure require treatment with a neuromuscular blocker, intubation and mechanical ventilation. Hyperthermia requires aggressive management. Rhabdomyolysis should be initially treated with IV fluids.

C) DECONTAMINATION

1) PREHOSPITAL: GI decontamination is not recommended because of the risk of aspiration.
2) HOSPITAL: Administration of activated charcoal and gastric lavage may be performed, if the patient presents early, but only after neuromuscular hyperactivity is controlled and the patient is intubated.

D) AIRWAY MANAGEMENT

1) Early endotracheal intubation should be performed in any patient with significant muscle spasms or convulsions.

E) ANTIDOTE

1) None.

F) HYPERTHERMIA

1) Aggressive control of muscle spasms and convulsions is paramount, and usually requires heavy sedation and neuromuscular paralysis. Remove patients clothing and encourage evaporative heat loss with fans and water to the skin. A cooling blanket or cool mist may be used to promote active cooling. Ice water immersion may be used in severe cases.

G) RHABDOMYOLYSIS

1) In cases of rhabdomyolysis secondary to neuromuscular hyperactivity, administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Monitor input and output, serum electrolytes, creatine kinase, and renal function.

H) ENHANCED ELIMINATION

1) Enhanced elimination is not indicated for strychnine poisoning. However, dialysis is indicated in cases of fluid overload, acid-base disturbances, and electrolyte abnormalities in patients with renal failure.

I) PATIENT DISPOSITION

1) HOME CRITERIA: All patients with significant exposures from strychnine should be transported by ambulance to a health care facility for evaluation and treatment.
2) ADMISSION CRITERIA: Patients with any systemic signs and symptoms (muscle spasms, rhabdomyolysis, hyperthermia) should be admitted to an intensive care setting and receive appropriate, aggressive care.
3) CONSULT CRITERIA: Consult a medical toxicologist or Poison center for assistance in managing any patients with signs and symptoms.

J) TOXICOKINETICS

1) Strychnine is rapidly absorbed following oral administration. It is also rapidly absorbed through the respiratory tract and intact skin. Onset of toxicity is generally within 5 minutes after intravenous or intranasal use, and within 15 minutes after ingestion. Muscle spasms and convulsions generally subside within 12 to 24 hours. As estimated by case reports and case series, strychnine follows first-order kinetics and has an approximate elimination half-life of 10 to 16 hours. Volume of distribution is estimated at 13 L/kg. It undergoes hepatic metabolism, with 10% to 20% eliminated unchanged in the urine.

K) DIFFERENTIAL DIAGNOSIS

1) Seizures and status epileptics, intoxication with sympathomimetics (eg, cocaine, amphetamines), tetanus, rhabdomyolysis. Strychnine poisoning can be distinguished from seizures because the patient remains awake during the convulsions. Because patients often remain alert during powerful and painful convulsions, this may produce panic.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Tachycardia, hypertension, tachypnea, and hyperthermia may be seen.
2) In severe cases, respiratory paralysis (apnea) with bradycardia, hypotension, and cardiac arrest may occur.

3.3.2)

A) WITH POISONING/EXPOSURE

1) HYPERPNEA: The respiratory rate is often increased with arterial blood gases showing a respiratory alkalosis. This may be secondary to agitation or compensatory response to the metabolic acidosis which results from seizures.
2) RESPIRATORY PARALYSIS: With severe or prolonged seizures, sustained contractions of the chest wall muscles and diaphragm may lead to respiratory paralysis. A period of flaccid paralysis with apnea and cyanosis may also occur in the immediate post convulsive period (Burn et al, 1989; Jackson et al, 1971; Loughhead et al, 1978). In these instances, arterial blood gases reveal a respiratory as well as metabolic acidosis (Burn et al, 1989; Dittrich et al, 1984; Boyd et al, 1983; Edmunds et al, 1986; Loughhead et al, 1978; O'Callaghan et al, 1982).

3.3.3)

A) WITH POISONING/EXPOSURE

1) HYPERTHERMIA: Hyperthermia may occur in patients with neuromuscular hyperactivity, particularly those with severe or prolonged seizures (Makarovsky et al, 2008; Oberpaur et al, 1999; Boyd et al, 1983; Dittrich et al, 1984; Edmunds et al, 1986). Temperatures as high as 43 degrees C have been reported (Boyd et al, 1983).

3.3.4)

A) WITH POISONING/EXPOSURE

1) HYPERTENSION has been reported (Makarovsky et al, 2008; Oberpaur et al, 1999; Boyd et al, 1983; Loughhead et al, 1978; Maron et al, 1971).
2) HYPOTENSION may also occur (Shadnia et al, 2004; Dittrich et al, 1984; Edmunds et al, 1986; O'Callaghan et al, 1982). It appears to be due to marked acidosis and hypoxia in patients with severe or prolonged convulsions.

3.3.5)

A) WITH POISONING/EXPOSURE

1) TACHYCARDIA: It commonly accompanies agitation and neuromuscular hyperactivity (Makarovsky et al, 2008; Boyd et al, 1983; Gordon & Richards, 1979; Burn et al, 1989; Loughhead et al, 1978; Maron et al, 1971).
2) BRADYCARDIA: Bradycardia and asystole may occur in severe cases (Burn et al, 1989; Dittrich et al, 1984; Edmunds et al, 1986; O'Callaghan et al, 1982). It may be seen in patients with respiratory arrest and appears to be due to severe hypoxia and acidosis.

Heent

3.4.1)

A) WITH POISONING/EXPOSURE

1) EYES: Bilateral horizontal pendular nystagmus and blurred vision have been reported.

3.4.3)

A) WITH POISONING/EXPOSURE

1) NYSTAGMUS: Bilateral, conjugate, horizontal, pendular nystagmus, unresponsive to diazepam, have been reported (Blain et al, 1982; Nishiyama & Nagase, 1995; Fernandez et al, 2000).
2) MYDRIASIS: Reactive, bilateral mydriasis was reported in a 6-year-old boy following ingestion of strychnine solution (480 mg) (Oberpaur et al, 1999). Mildly mydriatic pupils were reported in an adult with strychnine poisoning (Shadnia et al, 2004) .
3) BLURRED VISION and conjunctival edema have been reported (Oberpaur et al, 1999; Grant & Schuman, 1993; Boyd et al, 1983).

3.4.6)

A) WITH POISONING/EXPOSURE

1) POLYDIPSIA: Patients may complain of increased thirst (Polson et al, 1983).

Cardiovascular

3.5.2)

A) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) Hypertension and tachycardia have been reported (Scully et al, 2001; Oberpaur et al, 1999; Boyd et al, 1983; Gordon & Richards, 1979; Jackson et al, 1971; Loughhead et al, 1978; Maron et al, 1971).

B) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) Cardiac arrest may result from severe or prolonged seizures or respiratory arrest (Makarovsky et al, 2008; Burn et al, 1989; Dittrich et al, 1984; Edmunds et al, 1986; Jackson et al, 1971; O'Callaghan et al, 1982).

C) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) Bradycardia with hypotension and prolongation of the PR, QRS, and QT intervals were reported in a 51-year-old man who ingested 4.8 g of strychnine (Heiser et al, 1989).

D) ELECTROCARDIOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) Nonspecific ECG ST segment and T-wave abnormalities have been reported (Gordon & Richards, 1979).

E) VENTRICULAR ARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) A case of combined strychnine and aconitine poisoning occurred in a 29-year-old man resulting in nodal beats followed by multifocal ectopic ventricular beats deteriorating to ventricular tachycardia and finally fibrillation despite lidocaine therapy (Martens & Vandevelde, 1993).

F) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Mild hypertension has been reported (Oberpaur et al, 1999; Boyd et al, 1983; Loughhead et al, 1978; Maron et al, 1971).

Respiratory

3.6.2)

A) RESPIRATORY FAILURE

1) WITH POISONING/EXPOSURE

a) SUMMARY: Spasm or paralysis of the respiratory muscles may lead to respiratory compromise with hypoxia, cyanosis, hypercarbia, and respiratory acidosis (Shadnia et al, 2004; Boyd et al, 1983; Burn et al, 1989; Edmunds et al, 1986; Loughhead et al, 1978). Respiratory failure, which can occur within several hours of ingestion, may lead to cardiac arrest and is the primary cause of death (Baselt, 2000; Flood, 1999).

B) CYANOSIS

1) WITH POISONING/EXPOSURE

a) Cyanosis may occur in patients with seizures or respiratory arrest (Burn et al, 1989; Edmunds et al, 1986; Jackson et al, 1971; Loughhead et al, 1978; O'Callaghan et al, 1982).

C) HYPERVENTILATION

1) WITH POISONING/EXPOSURE

a) SUMMARY: Tachypnea may commonly accompany neuromuscular hyperactivity (Scully et al, 2001; Boyd et al, 1983; Maron et al, 1971).
b) CASE REPORT: Tachypnea, perioral numbness and carpopedal spasms, along with tonic contractions of limb muscles were seen in a 42-year-old woman following ingestion of 15 g "maqianzi", the dried ripe seed of Strychnos nux vomica. The patient improved within a few hours and was discharged home the next day (Chan, 2002).

D) DYSPNEA

1) WITH POISONING/EXPOSURE

a) Patients may complain of dyspnea, chest tightness, and a feeling of suffocation.

E) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Adult respiratory distress syndrome (ARDS) developed in a patient who had severe acidosis, rhabdomyolysis, and renal failure (Gordon & Richards, 1979).

F) PULMONARY EMBOLISM

1) WITH POISONING/EXPOSURE

a) A 34-year-old man developed a fatal massive pulmonary embolus, despite prophylactic heparin, following an overdose of 2.25 g of strychnine (Palatnick et al, 1997).

G) ASPIRATION PNEUMONIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT/PEDIATRIC: Aspiration pneumonia as evidenced by a positive sputum culture and lung infiltrate on chest x-ray was observed in a 6-year-old boy following accidental strychnine ingestion. The aspiration was thought to have occurred from severe muscle tetany experienced following the ingestion (Starretz-Hacham et al, 2003).
b) CASE REPORT/ADULT: A 28-year-old man developed recurrent seizures, rhabdomyolysis and acute oliguric renal failure after ingesting strychnine. On the second day of hospitalization he developed clinical evidence of aspiration pneumonia (Shadnia et al, 2004).

H) PULMONARY EDEMA

1) WITH POISONING/EXPOSURE

a) BRUCINE

1) POSTMORTEM: A 60-year-old man employed at a chemical plant was found dead in his apartment after ingesting and unknown amount of brucine. A container labeled "Brucine" and a glass with watery residue and substance traces were found near the body. An autopsy 12 hours postmortem revealed massive pulmonary edema and histologic evidence of kidney damage. Brucine was detected in the blood and various organs; drug and alcohol screens were negative (Teske et al, 2011).

Neurologic

3.7.2)

A) SEIZURE

1) WITH POISONING/EXPOSURE

a) ONSET: Seizures are common and may occur abruptly within 15 minutes of ingestion, within 5 minutes of intranasal insufflation, and within several minutes of intravenous injection.
b) TYPE: In contrast to epileptic seizures, strychnine-induced seizures are characterized by tonic/tetanic rather than tonic-clonic motor activity, and the patient usually maintains a clear sensorium during and after seizures, since strychnine has its predominant effect on the ventral horn motor neurons. This is of major diagnostic importance. If seizures are severe or prolonged, however, CNS acidosis or hypoxia develop and there may be loss of consciousness. Opisthotonic posturing is typical (Scully et al, 2001; Flood, 1999).

1) Complications are directly related to severity and frequency of seizures, and may include profound lactic acidosis, hyperthermia, rhabdomyolysis, and myoglobinuria and acute renal failure (Shadnia et al, 2004; Flood, 1999).

c) SITES: All muscle groups are subject to sustained contractions. Risus sardonicus and opisthotonus are characteristic. The position of the extremities is determined by the most powerful muscle group affecting a given joint.

1) In humans, flexion of the upper limbs and extension of the lower limbs is the typical posture.

a) CASE REPORT: A 34-year-old man developed increasing spasms, which worsened with stimulus, progressing to opisthotonic posturing and apnea following ingestion of an unknown quantity of strychnine. An attempt to insert an airway resulted in trismus (Dickson et al, 1992).

2) Animal posturing reflects contractions of the antigravity musculature, and the forelimbs, as well as the hindlimbs are typically in positioned extension.

d) PRODROME: Seizures may or may not be preceded by muscle cramps, spasms, tightness, and twitching.
e) DURATION: Seizures typically last 30 seconds to 2 minutes (Makarovsky et al, 2008) and are followed by a muscle relaxation interval of 5 to 10 minutes before the next seizures. Without treatment patients rarely survive more than 5 seizure episodes. In severe cases, seizures are sustained until terminated by respiratory and cardiac arrest (Flood, 1999). Prognosis is generally good if patients survive beyond 5 hours.
f) HYPERREFLEXIA: Before, between, and following seizures, patients typically have hyperreflexia with clonus, particularly in the lower extremities. Percussion of the muscles may cause spasm or twitching (Radosavljevic et al, 2006; Oberpaur et al, 1999).

1) CASE REPORT: Hyperreflexia with clonus was reported in a 34-year-old man following ingestion of an unknown quantity of strychnine (Dickson et al, 1992).

g) STIMULI: Any type of minor or faint auditory, tactile, or visual sensory stimulation (eg, physical movement, bright light) may precipitate a startle response, intense muscle spasms or seizures (Parker et al, 2011; Makarovsky et al, 2008; Oberpaur et al, 1999). Ongoing profound muscle spasms may lead to hypoxemia requiring intubation and mechanical ventilation (Parker et al, 2011).
h) PAIN: Seizures are painful and patients typically express great fear and apprehension of having subsequent episodes.
i) SEQUELAE: Neuromuscular sequelae in survivors is rare (Flood, 1999).
j) CASE REPORT: A 29-year-old man experienced repeated episodes of generalized tonic-clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, rhabdomyolysis, lactic acidosis, nonoliguric renal failure, and elevated LDH levels. He recovered completely following supportive care and was discharged on the 10th hospital day (Santhosh et al, 2003).
k) CASE REPORT: A 51-year-old man was transported to the ED within 15 minutes of ingestion of 4.8 g strychnine and immediately presented with a major motor seizure. Despite treatment with diazepam, pancuronium, and phenobarbital the patient continued to have jerking of the jaw and neck and died several days later (Heiser et al, 1992).

B) COMA

1) WITH POISONING/EXPOSURE

a) Loss of consciousness may follow severe or prolonged seizures and appears to result from CNS acidosis and hypoxia (Boyd et al, 1983; Burn et al, 1989; Edmunds et al, 1986; Jackson et al, 1971; Loughhead et al, 1978).
b) CASE REPORT: A 51-year-old man ingested 4.8 g of strychnine, and collapsed in the ED following a seizure within 15 minutes of exposure and never regained consciousness. Neurological examination several days later, after all sedating medications had been withdrawn, revealed a deeply comatose patient with a severe, diffuse encephalopathy (Heiser et al, 1992).

C) NYSTAGMUS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Varying nystagmus with horizontal or vertical eye movement was observed in a 68-year-old man following a suicide attempt with a rodenticide containing strychnine (Nishiyama & Nagase, 1995).

D) HEADACHE

1) WITH POISONING/EXPOSURE

a) Headache has been reported (Boyd et al, 1983).

Gastrointestinal

3.8.2)

A) VOMITING

1) WITH POISONING/EXPOSURE

a) Nausea and vomiting may occur but it is not common (Makarovsky et al, 2008; Boyd et al, 1983; Burn et al, 1989; Fernandez et al, 2000; Starretz-Hacham et al, 2003).

B) PANCREATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Pancreatitis was reported in an 18-year-old woman following accidental ingestion of "rat biscuit" containing strychnine. Serum amylase increased from admission (227 Units/L) to a peak of 1004 Units/L by day 13, with urine amylase reported to be 2273 Units/L. Serum glucose never rose higher than 147 mg/dL. Abdominal ultrasonography revealed pancreatic size and structure to be normal (Hernandez et al, 1998).

Hepatic

3.9.2)

A) HEPATIC NECROSIS

1) WITH POISONING/EXPOSURE

a) Multiple organ failure, including hepatic necrosis has been reported in a patient with hyperthermia (Gordon & Richards, 1979).

B) LIVER ENZYMES ABNORMAL

1) WITH POISONING/EXPOSURE

a) SUMMARY: Increased liver enzyme levels may be noted following strychnine poisoning.
b) CASE REPORT: A 29-year-old man experienced repeated episodes of generalized tonic-clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, rhabdomyolysis, lactic acidosis, nonoliguric renal failure, and elevated LDH levels (250 Units/L, normal 100-190 Units/L). He recovered completely following supportive care and was discharged on the 10th hospital day (Santhosh et al, 2003).
c) CASE REPORT: Hernandez et al (1998) reported alkaline phosphatase, GGT, and ALT levels of 380 Units/L, 263 Units/L, and 251 Units/L, respectively, which peaked at 10 days following the accidental ingestion of an unknown quantity of strychnine in an 18-year-old woman (Hernandez et al, 1998).
d) CASE REPORT: Nishiyama & Nagase (1995) reported increased serum LDH, SGOT and SGPT levels following ingestion of a strychnine-containing rodenticide in a 68-year-old man (Nishiyama & Nagase, 1995a).
e) CASE REPORT: van Heerden et al (1993) reported SGOT serum levels of 800 International Units/L in a 55-year-old man following ingestion of 300 to 400 mg strychnine (van Heerden et al, 1993).

Genitourinary

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) Rhabdomyolysis with consequent myoglobinuric renal failure is common in patients who have strychnine-induced seizures (Makarovsky et al, 2008; Shadnia et al, 2004; Boyd et al, 1983; Dittrich et al, 1984; Edmunds et al, 1986; Gordon & Richards, 1979). Renal failure may be polyuric as well as oliguric.
b) An increased serum creatinine with a normal BUN may result from rhabdomyolysis (Boyd et al, 1983). If renal failure develops, both the creatinine and BUN are elevated.
c) CASE REPORT: A 29-year-old man experienced repeated episodes of generalized tonic clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, rhabdomyolysis (CPK 89360 Units/L; normal 0-190 Units/L), lactic acidosis, nonoliguric renal failure (urea: 91 mg/dL; serum creatinine: 4.7 mg/dL) and elevated LDH levels. He recovered completely following supportive care and was discharged on the 10th hospital day (Santhosh et al, 2003).
d) CASE REPORT/BRUCINE: A 24-year-old man drank a decoction made from the bark of the Strychnos nux vomica tree (which contains brucine, a less potent alkaloid of strychnine) for a religious ceremony and developed convulsions within a few minutes. By day 5, the patient developed acute renal failure and rhabdomyolysis (CPK 7182 International Units/L); clinical improvement occurred with hemodialysis therapy. In 2 weeks, the patient completely recovered (Naik & Chakrapani, 2009).

B) ELECTROLYTES ABNORMAL

1) WITH POISONING/EXPOSURE

a) Acidosis, hyperkalemia, hypocalcemia, and hypophosphatemia may result from rhabdomyolysis and acute renal failure (Boyd et al, 1983; Edmunds et al, 1986; Gordon & Richards, 1979).

C) MYOGLOBINURIA

1) WITH POISONING/EXPOSURE

a) Myoglobinuria may give the urine a reddish color and result in a false positive orthotoluidine reaction for occult blood (hemoglobin).
b) Serum myoglobin levels of greater than 500 ng/mL on day one of strychnine poisoning in a 68-year-old man were reported. Levels decreased to 350 ng/mL on day 3 and 13 ng/mL on day 4 (Nishiyama & Nagase, 1995).
c) CASE REPORT: A 29-year-old man experienced repeated episodes of generalized tonic-clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, rhabdomyolysis (CPK 89360 Units/L; normal 0-190 Units/L), lactic acidosis, nonoliguric renal failure and elevated LDH levels. He recovered completely following supportive care and was discharged on the 10th hospital day (Santhosh et al, 2003).

D) URINARY CASTS

1) WITH POISONING/EXPOSURE

a) Granular casts were seen on microscopic urinalysis of one patient with myoglobinuric renal failure (Boyd et al, 1983).

E) CRYSTALLURIA

1) WITH POISONING/EXPOSURE

a) Microscopic crystals were found in the urine of a 32-year-old farmer. Further analysis of blood and urine identified a compound with migration and staining characteristics of strychnine by thin layer chromatography techniques (Burn et al, 1989).

Acid-Base

3.11.1)

A) Both metabolic (lactic) and respiratory acidosis may be noted.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) INCIDENCE: Metabolic acidosis is universally seen in patients with seizures. Serum pHs of 7.0 are typical, and those in the 6.6 range are not uncommon. Patients have recovered fully in spite of severe acidosis (Boyd et al, 1983; Edmunds et al, 1986; Dittrich et al, 1984; Goldstein, 1975; Lambert et al, 1981; Loughhead et al, 1978; Dickson et al, 1992; Hernandez et al, 1998).
b) PATHOGENESIS: Metabolic acidosis results from lactic acidemia secondary to neuromuscular hyperactivity and hypoxia. It is characterized by an increased anion gap and low serum bicarbonate (Boyd et al, 1983; Dittrich et al, 1984; Lambert et al, 1981). Lactic acidosis generally resolves without specific treatment once seizures have been controlled (Boyd et al, 1983).
c) Metabolic acidosis may also result from acute renal failure (Gordon & Richards, 1979).
d) CASE REPORT: A 29-year-old man experienced repeated episodes of generalized tonic clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, lactic acidosis (pH7.28; PaCO2 32 mm Hg; PaO2 8.6 mm Hg; HCO3 13.5 mmols), and nonoliguric renal failure. He recovered completely following supportive care and was discharged on the tenth hospital day (Santhosh et al, 2003).

B) RESPIRATORY ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Seizures may impair respirations or lead to apnea resulting in hypercarbia and respiratory acidosis as well as metabolic acidosis (Edmunds et al, 1986; Burn et al, 1989; Jackson et al, 1971; Loughhead et al, 1978).

C) RESPIRATORY ALKALOSIS

1) WITH POISONING/EXPOSURE

a) Agitation may be accompanied by tachypnea and a respiratory alkalosis.
b) Metabolic acidosis may be accompanied by a compensatory respiratory alkalosis (Boyd et al, 1983).

Hematologic

3.13.2)

A) LEUKOCYTOSIS

1) WITH POISONING/EXPOSURE

a) Leukocytosis is common in patients with seizures. The WBC may be as high as 49,300 (Boyd et al, 1983).

1) CASE REPORT: Nishiyama & Nagase (1995) reported a case of strychnine poisoning in a 68-year-old man that resulted in a white blood cell (WBC) count of 20,600/mm(3) within 24 hours and Hernandez et al (1998) reported a WBC of 45,960/mm(3) within a few hours in an accidental ingestion in an 18-year-old woman.

Dermatologic

3.14.2)

A) EXCESSIVE SWEATING

1) WITH POISONING/EXPOSURE

a) Diaphoresis may be noted and is sometimes profuse (Boyd et al, 1983; Polson et al, 1983).

Musculoskeletal

3.15.2)

A) RHABDOMYOLYSIS

1) WITH POISONING/EXPOSURE

a) SUMMARY

1) Rhabdomyolysis with increased serum creatine phosphokinase (CPK) is common in patients who have strychnine-induced seizures (Shadnia et al, 2004; Edmunds et al, 1986; Hernandez et al, 1998; Scully et al, 2001; Starretz-Hacham et al, 2003).

b) CASE REPORTS

1) One patient with rhabdomyolysis had a serum creatine kinase (CK) level of 359,000, a serum uric acid level of 31.6 mg/dL, and urine myoglobin level of 124 mg/dL after snorting two lines of strychnine (thought to be cocaine) (Boyd et al, 1983).
2) Increased serum creatinine and uric acid and either increased or decreased serum calcium, phosphate, and potassium may be seen in patients with rhabdomyolysis.
3) Palatnick et al (1995) and Palatnick et al (1997) report the case of a 34-year-old male who presented to the ED following an ingestion of 2.25 g strychnine and exhibiting muscle spasms. His condition deteriorated and mild rhabdomyolysis ensued (peak creatine kinase 9,965 Units/L). After recovering from rhabdomyolysis he died from a massive pulmonary embolus (Palatnick et al, 1995; Palatnick et al, 1997).
4) Rhabdomyolysis, with serum (CPK) increasing from 3820 Units/L on admission to 22600 Units/L 3 days later is reported in an 18-year-old woman following an accidental ingestion of strychnine. The patient had presented with generalized tonic-clonic seizures, stiffness and violent muscle spasms. Metabolic acidosis was present (Hernandez et al, 1998).
5) A 29-year-old man experienced repeated episodes of generalized tonic clonic seizures and muscle spasms after ingesting an unknown volume of Dogkill (5% strychnine). He developed myoglobinuria, rhabdomyolysis (CPK 89360 Units/L; normal 0-190 Units/L), lactic acidosis, and nonoliguric renal failure and elevated LDH levels. He recovered completely following supportive care and was discharged on the 10th hospital day (Santhosh et al, 2003).
6) CASE REPORT/BRUCINE: A 24-year-old man drank a decoction made from the bark of the Strychnos nux vomica tree (which contains brucine, a less potent alkaloid of strychnine) for a religious ceremony and developed convulsions within a few minutes. By day 5, the patient developed acute renal failure and rhabdomyolysis (CPK 7182 International Units/L); clinical improvement occurred with hemodialysis therapy. In 2 weeks, the patient completely recovered (Naik & Chakrapani, 2009).

B) TETANY

1) WITH POISONING/EXPOSURE

a) SUMMARY: Muscle tenderness, pain, and edema may be noted after seizures. Trismus, risus sardonicus, and opisthotonus are also characteristic.
b) CASE REPORT: Severe muscle cramps and vomiting were the first symptoms reported in a 6-year-old boy who ingested a strychnine tablet. Upon admission to the hospital, the boy had generalized muscle tetany and later developed rhabdomyolysis (Starretz-Hacham et al, 2003).

C) COMPARTMENT SYNDROME

1) WITH POISONING/EXPOSURE

a) Median nerve compression from muscle edema and an increased anterior tibial compartment pressure with foot drop have been reported in a patient with severe seizures (Boyd et al, 1983).

Reproductive

3.20.1)

A) Pre-implantation mortality and stillbirth were observed in rats.

3.20.2)

A) STILLBIRTH

1) RATS - Pre-implantation mortality and stillbirth were observed in rats (RTECS , 2001).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS57-24-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs, including continuous monitoring of core temperature in any patient with muscle spasms.
B) Monitor serum electrolytes, creatine kinase, renal function, liver enzymes, urinalysis and urine output in symptomatic patients.
C) Strychnine can be found in the urine, blood, gastric fluids, and other organs, but the levels do not correlate well with clinical toxicity or need for therapy and are not readily available.
D) Symptomatic patients should be on a continuous cardiac monitor and have an ECG performed.

4.1.2)

A) TOXICITY

1) Levels do not correlate with clinical toxicity and the need for therapy. Toxicity has been reported at 0.1 mg/100 mL.

B) BLOOD/SERUM CHEMISTRY

1) Monitor BUN, creatinine, electrolytes, calcium, magnesium, phosphorus, phosphocreatine kinase (CPK), SGOT, and LDH.

C) ACID/BASE

1) Arterial blood gases are necessary to assess acid-base status and pulmonary/respiratory function.

4.1.3)

A) URINALYSIS

1) Monitor urine output, and urinalysis to assess for rhabdomyolysis and renal dysfunction.

B) URINARY LEVELS

1) Strychnine is excreted in the urine and can be detected there for 24 hours or more following exposure.
2) Quantitative urine levels are not helpful in assessing severity or determining treatment.

4.1.4)

A) OTHER

1) POSTMORTEM

a) SUMMARY: In fatal cases, strychnine has been detected in virtually all organs (Baselt & Cravey, 1989; Perper, 1985; Winek et al, 1986). Relatively high levels are found in the liver and in bile.
b) CASE REPORT: In a 56-year-old man suicide fatality, levels were highest in the stomach contents (175 mg/L), stomach wall (14.9 mg/L), bile (9.2 mg/L), and liver (6.2 mg/L) (Perper, 1985; Winek et al, 1986).

2) MONITORING

a) Monitor vital signs including temperature. Continuous temperature monitoring by rectal probe is advised if hyperthermia is noted.

Methods

1) Strychnine can be detected in the urine, blood, gastric aspirate, and other organs by colorimetry or ultraviolet spectrophotometry (Darawy & Tompsett, 1956; Bogan et al, 1966), but gas-liquid chromatography with a flame ionization detector (FID) (Winek et al, 1986), gas chromatography (Oliver et al, 1979), and high-performance liquid chromatography (Alliot et al, 1982) are more sensitive and specific.
2) Rosano et al (2000) described the application of gas chromatography and tandem ion-trap mass spectrometry for detection and quantification of strychnine in postmortem body fluids and tissues (Rosano et al, 2000).
3) Brucine was detected and quantified in postmortem blood, gastric contents and various organs using liquid-chromatography-tandem mass spectrometry. Based on a solid-phase extraction for human serum, the validation process indicated limits of detection and quantification of 0.12 and 0.23 ng/mL, respectively (Teske et al, 2011).
4) Strychnine and brucine were detected in postmortem blood and gastric contents using reversed phase HPLC with diode-array detection. The limit of quantitation was 5 ng/mL blood for both strychnine and brucine. More conventional techniques such as GC-MS had failed to detect strychnine in this case (Wang et al, 2004).
5) Liquid chromatography with photodiode array detection was used to determine strychnine concentration in blood, gastric contents, and adulterated beer. This method allowed detection with only 0.1 mL of sample (Duverneuil et al, 2004).

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with any systemic signs and symptoms (muscle spasms, rhabdomyolysis, hyperthermia) should be admitted to an intensive care setting and receive appropriate, aggressive care.

6.3.1.2) HOME CRITERIA/ORAL

A) All patients with significant exposures from strychnine should be transported by ambulance to a health care facility for evaluation and treatment.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or Poison center for assistance in managing any patients with signs and symptoms.

6.3.1.4) PATIENT TRANSFER/ORAL

A) Patients who require admission and must be transferred should be accompanied by personnel certified in ACLS and capable of performing endotracheal intubation and cardiac resuscitation.
B) Attendants should also be knowledgeable regarding the intravenous use of diazepam, phenobarbital, and neuromuscular blockers.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) All patients with accidental or intentional strychnine ingestions require at least 4 hours of observation.
B) Patients who remain asymptomatic or have minor toxicity and become asymptomatic during a 4- to 6-hour observation period may be discharged.

Monitoring

Oral Exposure

6.5.1)

A) GI DECONTAMINATION/NOT RECOMMENDED

1) GI decontamination is not recommended because of the risk of aspiration.

6.5.2)

A) GASTRIC LAVAGE

1) Gastric lavage or nasogastric intubation for the purpose of activated charcoal administration should be performed only after control of neuromuscular hyperactivity and assurance of an airway and adequate respirations. These procedures could precipitate a seizure and lead to reflux of gastric contents with pulmonary aspiration if the airway is not protected.

B) ACTIVATED CHARCOAL

1) Activated charcoal may be administered, if the patient presents early, but only after neuromuscular hyperactivity is controlled and the patient is intubated. Activated charcoal is extremely effective in adsorbing strychnine.

a) One gram of activated charcoal is capable of binding 950 mg of strychnine (Anderson, 1946). The oral LD50 of strychnine in mice was increased 410 times when activated charcoal was given concurrently (Olkkola, 1984). The oral LD50 of strychnine in rats increased 3- to 4-fold when activated charcoal was given 30 seconds after a dose of strychnine (Picchioni et al, 1966).

2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) SUPPORT

1) Treatment is basically symptomatic and supportive with emphasis on controlling neuromuscular hyperactivity, performing endotracheal intubation and providing mechanical ventilation as necessary, preventing and correcting metabolic acidosis and electrolyte abnormalities, preventing and correcting myoglobinuric renal failure, cooling measures for hyperthermia, and giving activated charcoal to prevent enteral strychnine absorption.

B) MONITORING OF PATIENT

1) Monitor vital signs, including continuous monitoring of core temperature in any patient with muscle spasms.
2) Monitor serum electrolytes, creatine kinase, renal function, liver enzymes, urinalysis and urine output in symptomatic patients.
3) Arterial blood gases are necessary to assess acid-base status and pulmonary/respiratory function.
4) Strychnine is found in urine, blood gastric fluid, and other organs, but the levels do not correlate well with clinical toxicity or need for therapy and are not readily available.
5) Symptomatic patients should be on a continuous cardiac monitor and have an ECG performed.

C) AIRWAY MANAGEMENT

1) Administer supplemental oxygen and assist ventilation.
2) Treat seizures and neuromuscular hyperactivity with benzodiazepines and barbiturates or propofol.
3) Initiate neuromuscular paralysis and perform endotracheal intubation, if above measures are unsuccessful.
4) Monitor arterial blood gases and/or oxygen saturation.

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (diazepam or lorazepam). If seizures persist or recur administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or treat with intravenous dextrose ADULT: 100 milligrams IV, CHILD: 2 milliliters/kilogram 25% dextrose).

2) DIAZEPAM

a) Diazepam is considered the agent of choice for the treatment of seizures and neuromuscular hyperactivity (Boyd et al, 1983; Edmunds et al, 1986; Herishanu & Landau, 1972; Gordon & Richards, 1979; Lambert et al, 1981; Maron et al, 1971; O'Callaghan et al, 1982).
b) Higher than usual doses of diazepam may be necessary to control seizures. Assist respirations and perform endotracheal intubation for airway protection if the level of consciousness becomes depressed.
c) Diazepam has also been administered as continuous intravenous infusion (Dittrich et al, 1984).
d) DIAZEPAM

1) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
2) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
3) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

e) NO INTRAVENOUS ACCESS

1) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
2) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

3) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

4) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

5) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

6) RECURRING SEIZURES

a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:

1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)

b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

7) Although other barbiturates such as aprobarbital (Sgaragli & Mannaioni, 1973) and thiopental (Boyd et al, 1983; Edmunds et al, 1986; Sgaragli & Mannaioni, 1973) have been used, the higher anesthesia to anticonvulsant ratio of phenobarbital make it the barbiturate of choice (Boyd et al, 1983).

E) NEUROMUSCULAR BLOCKER

1) SUMMARY

a) Neuromuscular blockade and endotracheal intubation will be necessary in severe poisonings (recurrent muscle spasms, respiratory failure, hyperthermia). Non-depolarizing agents are preferred because most of these patients will have rhabdomyolysis and hyperkalemia.
b) Succinylcholine appears to be safe but has the disadvantage of potentially worsening rhabdomyolysis and hyperthermia. It should therefore be used only to facilitate intubation.
c) Pancuronium (Boyd et al, 1983; O'Callaghan et al, 1982), vecuronium (Oberpaur et al, 1999), d-tubocurarine (Sgaragli & Mannaioni, 1973), succinylcholine (Edmunds et al, 1986) (Lambert et al, 1981), and suxamethonium (O'Callaghan et al, 1982) have all been used for neuromuscular paralysis.

F) BODY TEMPERATURE ABOVE REFERENCE RANGE

1) Control seizures and neuromuscular hyperactivity. Undress patient and enhance evaporative heat loss by directing fans on patient and applying water to the skin. Cooling blankets, and ice water immersion may be needed in more severe cases. Cardiopulmonary bypass should be considered in severe or refractory cases.
2) Antipyretics are not effective.
3) Control of seizures and neuromuscular hyperactivity is an essential part of treatment.
4) Monitor core temperature continuously.

G) RHABDOMYOLYSIS

1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).

H) ACIDOSIS

1) Control of seizures and neuromuscular hyperactivity and correction of hypoxia is necessary to prevent continued lactate production.
2) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
3) Large doses of sodium bicarbonate may be required (Boyd et al, 1983; Dittrich et al, 1984; Edmunds et al, 1986).

I) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

J) HYPERTENSIVE EPISODE

1) Hypertension is not life-threatening and does not require specific therapy. It usually resolves following control of neuromuscular hyperactivity.

K) TACHYARRHYTHMIA

1) Tachycardia is not life-threatening and does not require specific therapy. It usually resolves following control of neuromuscular hyperactivity.

L) BRADYCARDIA

1) Evaluate for hypoxia and acidosis. Administer oxygen and manage airway as clinically indicated.
2) ATROPINE

a) ATROPINE/DOSE

1) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
2) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

a) There is no minimum dose (de Caen et al, 2015).
b) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

3) ISOPROTERENOL

a) ISOPROTERENOL INDICATIONS

1) Used for temporary control of hemodynamically significant bradycardia in a patient with a pulse; generally other modalities (atropine, dopamine, epinephrine, dobutamine, pacing) should be used first because of the tendency to develop ischemia and dysrhythmias with isoproterenol (Neumar et al, 2010).
2) ADULT DOSE: Infuse 2 micrograms per minute, gradually titrating to 10 micrograms per minute as needed to desired response (Neumar et al, 2010).
3) CAUTION: Decrease infusion rate or discontinue infusion if ventricular dysrhythmias develop(Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
4) PEDIATRIC DOSE: Not well studied. Initial infusion of 0.1 mcg/kg/min titrated as needed, usual range is 0.1 mcg/kg/min to 1 mcg/kg/min (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

M) RENAL FAILURE SYNDROME

1) Initiate dialysis as necessary to control fluid, acid-base, and electrolyte abnormalities.
2) Monitor urine output, BUN, and serum electrolytes, calcium, magnesium, phosphorus, and creatinine.

N) EXPERIMENTAL THERAPY

1) Methysticine a kavalactone contained in Kava (Piper methysticum), has been shown to prevent strychnine toxicity. The mechanism of action was studied in a mouse model, and it was determined that methysticine protection against seizures may be mediated via local anesthetic effects (but not GABA receptors tested or glycine). It appears to be effective in preventing seizures produced by a Na+ channel-opener, thus it may be effective therapy for strychnine poisoning (Palmer et al, 1999).

Enhanced Elimination

1) Insufficient data to assess the clinical or pharmacological efficacy of dialysis following strychnine intoxication.
2) Dialysis may be necessary to correct acid-base, electrolyte, and metabolic abnormalities refractory to other measures.

1) The efficacy of a forced acid diuresis to enhance the renal elimination of strychnine is questionable and no longer is recommended. Acid diuresis should be avoided in the presence of rhabdomyolysis and associated myoglobinuria since an acidic urine may precipitate myoglobin in the renal tubules and lead to renal insufficiency.

Abstracts

Case Reports

1) ACUTE EFFECTS

a) FATALITY: A 32-year-old farmer vomited and had a series of tonic seizures thirty minutes after removing farm equipment from their nearby barn that was on fire. After several seizures he became cyanotic and lost consciousness in the field . On arrival at the health care facility he appeared well perfused and was no longer cyanotic. He had sinus tachycardia and was given diazepam, paralyzed and intubated. Metabolic acidosis (pH 6.6, pCO2 7.91 kPa, PO2 38.2 kPa on 100% O2 by mask) was treated with 200 mL of 8.4% IV sodium bicarbonate. Urine output remained less than 15 mL/hr. He was transferred to another facility for dialysis. Microscopic crystals were found in the urine. They were not oxalate and ethylene glycol was not detected in plasma. Thin layer chromatography identified a compound with migration and staining characteristics of strychnine. This was confirmed by GC/MS. This patient died 6 days later despite regular dialysis and continued ventilation. No source of poisoning was identified (Burn et al, 1989).
b) FATALITY: A 51-year-old man ingested 4.8 g of strychnine in a suicide attempt . In the Emergency Department 15 minutes later, he had a generalized seizure and was intubated and given activated charcoal with cathartic. Seizures continued for the next 48 hours and were treated with diazepam, pancuronium, and phenobarbital. Initially, his course was complicated by severe acidosis (pH 6.81), bradycardia, hypotension, hypocalcemia (7.6 mg/dL), and prolongation of the PR, QRS, and QT intervals. The initial blood level 30 minutes postingestion was 3.8 mg/L. Serial blood levels showed first-order elimination with a half-life of 10.8 hours. An EEG done 6 days postingestion showed generalized slowing consistent with severe diffuse encephalopathy. Despite supportive care, the patient died 8 days postingestion (Heiser et al, 1989).
c) SURVIVAL: A 19-year-old man developed nervousness, myalgias, intermittent uncontrollable muscle twitching, and prolonged symmetric extensor spasms 15 to 30 minutes after intranasally "snorting two lines" of strychnine, which he believed to be cocaine. Vital signs were: pulse 150 beats per minute, blood pressure 150/50 mmHg, respirations 35 per minute, and temperature 39.5 degrees C. Arterial blood gases revealed pH 6.55, pCO2 55 mmHg (7.9 kPa) and pO2 241 mmHg (32.1 kPa) on 100% oxygen. The WBC was 49300/mm(3), the serum bicarbonate was 4 mM/liter, the serum lactate level was 32 mM/liter, and the uric acid level was 31.6 mg/dL (1.8 mM/L). His temperature rose to 43 degrees C and he became cyanotic during muscle spasms. Muscle spasms were not controlled by 12 mg diazepam given IV so he was intubated, paralyzed using pancuronium, and mechanically ventilated. He developed rhabdomyolysis with a peak serum creatine kinase of 359,000, urine myoglobin 125 mg/dL, and peak serum creatinine and BUN levels of 3.7 mg/dL (327 mM/L) and 16 mg/dL in (5.7 mM/L), respectively. He also developed myoedema resulting in right hand and left foot weakness due to elevated compartment pressures (Boyd et al, 1983).
d) FATALITY: A 27-year-old man developed generalized, intermittent tetanic seizures after ingesting an unknown quantity of strychnine. Initial vital signs were blood pressure 110/70 mmHg, pulse 150/minute, respirations absent, and temperature 39.4 degrees C. Arterial blood gases on 100% oxygen showed pH 6.6; pCO2 52 mmHg; and pO2 233 mmHg. Laboratory abnormalities included serum bicarbonate of 4 mEq/L, sodium 151 mEq/L, glucose 373 mg/dL, phosphorus of 8.6 mg/dL, and creatinine of 1.7 mg/dL. The WBC was 21000/mm(3) and the lactate to pyruvate ratio was 57.5/3.5 (mg/dL). The ECG showed nonspecific ST and T wave changes. Intravenous diazepam (50 mg; 0.45 mg/kg) and sodium bicarbonate (7 amps) were given without effect. Following resuscitation from cardiac arrest, IV diazepam (120 mg; 0.9 mg/kg), phenobarbital (240 mg), and pancuronium (4 mg) were successful in stopping seizures, but the patient developed rhabdomyolysis, acute renal failure, ARDS, and hepatic neurosis. His course was further complicated by a cerebrospinal fluid leak and purulent sphenoid sinusitis secondary to a basilar skull fracture presumably sustained during seizures. He died 6 days after admission (Gordon & Richards, 1979).

Range Of Toxicity

Summary

Therapeutic Dose

7.2.1)

A) GENERAL

1) Doses of 1.5 milligrams have been used to treat impotence, but are no longer used (Savion et al, 1987).

7.2.2)

A) DISEASE STATE

1) For the treatment of glycine encephalopathy (nonketotic hyperglycinemia), oral dose of 200 micrograms/kilogram/day in 4 divided doses (Chien et al, 1978) and 0.8 milligram/kilogram/day (Haan et al, 1986) and intravenous doses of 600 micrograms/kilogram/day (Sankaran et al, 1982) have been used. This treatment regimen is no longer used.

Minimum Lethal Exposure

1) PEDIATRIC: When ingested, 5 to 10 mg in a small child may produce a lethal effect (Arena, 1962).
2) ADULT: Minimum lethal oral doses in adults reported in the literature range from 30 to 120 mg (Makarovsky et al, 2008).

a) Reported adult lethal dose may range from 100 to 120 mg (Palatnick et al, 1995).

3) ROUTE OF EXPOSURE: The lethal dose following intranasal, intravenous, and subcutaneous use is probably lower.
4) ONSET: Since the onset of symptoms is within 15 to 60 minutes following ingestion, determination of minimum lethal dose is of no value in determining probable clinical course. Determination of need to treat should be made on a clinical basis. Most deaths occur during the first 3 to 6 hours, and are commonly due to asphyxia.

1) During a religious ceremony, 6 members of a family drank a decoction from the bark of the Strychnos nux vomica tree. Each person was poisoned and 2 young children died. Three adults developed mild muscular spasms and stiffness, while a young man developed acute renal failure and rhabdomyolysis. He recovered after receiving hemodialysis therapy (Naik & Chakrapani, 2009).

Maximum Tolerated Exposure

1) The exposure limit is approximately 0.15 mg/m(3).
2) No toxicity is reported from strychnine accumulation; its detoxification and excretion occur quickly. Prognosis is good, if supportive treatment is maintained for the first 6 to 12 hours (Oberpaur et al, 1999).

1) ADULT

a) An adult ingested 3.75 g and survived (Cotten & Lane, 1966).

2) PEDIATRIC

a) An herbal product containing, 2 mg of strychnine produced symptoms of spasms in all limbs occurring every 5 to 10 minutes in a 4-year-old girl (Kulkarni & Holla, 1989).
b) A 6-year-old boy survived an ingestion of 480 mg (24 mg/kg) of a strychnine solution. The patient arrived at the hospital 15 minutes after the ingestion and was immediately given diazepam and thiopental, followed by intubation, mechanical ventilation and a continuous vecuronium infusion. He was discharged to home 33 hours after admission. No permanent sequelae was reported at his 6 month follow-up (Oberpaur et al, 1999).
c) Another 6-year-old boy experienced vomiting, severe muscle tetany and rhabdomyolysis following an ingestion of a 140 mg strychnine tablet. No effect was observed with early IV diazepam 0.5 mg/kg/dose treatment. The child was then paralyzed using a vecuronium bromide intravenous infusion of 0.1 mg/kg/hour, intubated and mechanically ventilated. After 20 hours, symptoms improved. He was discharged in good condition after 3 days(Starretz-Hacham et al, 2003).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CASE REPORTS

a) FATALITIES: Strychnine blood levels have ranged from 0.5 to 90 mcg/mL in fatal poisonings (Baselt & Cravey, 1989a; Winek et al, 1986). An adult intentionally poisoned himself with strychnine (a mole poisoning containing 10% strychnine with methylene blue to avoid accidents) and had a postmortem serum and gastric concentrations of 0.29 mcg/mL and 12.2 mcg/mL, respectively (Prat et al, 2015).
b) Survival has been reported in a patient with a blood strychnine level of 1.6 mcg/mL (Edmunds et al, 1986).
c) Peak serum strychnine concentration, occurring 3 hours after a 2.25 g ingestion in a 34-year-old man, was reported to be 2.1 mg/L (Palatnick et al, 1997).
d) A serum strychnine level of 2.17 mg/L has been reported approximately 6 hours following ingestion of an unknown quantity in an 18-year-old woman who recovered completely after 20 hospital days (Hernandez et al, 1998).
e) A 35-year-old woman developed a sudden onset of abnormal behavior and within a few minutes of presentation developed marked tremors, muscular spasms and seizures followed a short time later by respiratory and cardiac arrest. Despite immediate intubation and ventilation, the patient died a few hours later. Upon autopsy )2 hours after death), strychnine was isolated in the blood (2.14 mg/mL) , stomach contents (137 mg/kg wet weight), liver (91 mg/kg wet weight) and urine (2.35 mg/mL). The woman had ingested a capsule thought to be an antibiotic that was adulterated with strychnine. Her spouse had access to the chemical at work and was later convicted of the homicide (Kodikara, 2012).

2) BRUCINE

a) POSTMORTEM: Brucine, an alkaloid of strychnine, was detected in the blood and internal organ tissue of a 60-year-old man who was found dead after intentionally ingesting an unknown amount of the substance. Concentrations of brucine were quantified approximately 12 hours postmortem with the following results (Teske et al, 2011):

1) Femoral blood: 1510 ng/mL
2) Heart blood: 4470 ng/mL
3) Urine: 1685 ng/mL
4) Bile: 9936 ng/mL
5) Liver: 16,443 ng/g
6) Cerebellum: 988 ng/g
7) Cerebrum: 746 ng/g
8) Gastric contents: 1949 mcg/g (stomach contents 310 g = 604 mg brucine)

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Strychnine

a) TLV:

1) TLV-TWA: 0.15 mg/m(3)
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: Not Listed
2) Codes: Not Listed
3) Definitions: Not Listed

c) TLV Basis - Critical Effect(s): CNS impair
d) Molecular Weight: 334.4

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS57-24-9 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Strychnine
2) REL:

a) TWA: 0.15 mg/m(3)
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

3) IDLH:

a) IDLH: 3 mg/m3
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS57-24-9 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Strychnine
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Strychnine
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Strychnine
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS57-24-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Strychnine
2) Table Z-1 for Strychnine:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 0.15

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 2001 Budavari, 1996 Sax & Lewis, 1989

1) LD50- (INTRAMUSCULAR)MOUSE:

a) 628 mcg/kg

2) LD50- (INTRAPERITONEAL)MOUSE:

a) 980 mcg/kg

3) LD50- (ORAL)MOUSE:

a) 2 mg/kg

4) LD50- (SUBCUTANEOUS)MOUSE:

a) 474 mcg/kg

5) LD50- (INTRAMUSCULAR)RAT:

a) 1400 mcg/kg

6) LD50- (INTRAPERITONEAL)RAT:

a) 1100 mcg/kg

7) LD50- (ORAL)RAT:

a) 2350 mcg/kg
b) 16 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

Physicochemical

Physical Characteristics

Ph

Molecular Weight

Other

1) Odorless (CHRIS , 2002)

Animal Toxicology

Clinical Effects

11.1.3)

A) Dogs ingest strychnine in baits set for coyotes. These patients usually present with severe continuing tonic-clonic seizures which may be difficult to control.
B) CASE REPORT - Muscle tenseness, slight opisthotonus, regurgitation, salivation, mydriasis, dyspnea and cyanosis were seen in a 30 kg male German shepherd 10 hours after the dog was found after being loose for one hour. The dog died 15 minutes following the onset of clinical symptoms. Abnormal muscle movements or tetany was not observed.

1) Strychnine was confirmed by mass spectrometry/gas chromatography in the urine and stomach contents.
2) This case presents an atypical time course with delayed onset of symptoms. Previous studies in dogs, cats, horses and humans report the onset of initial symptoms to be within five to fifteen minutes (Meiser & Hagedorn, 2002).

11.1.5)

A) CASE REPORT - Six horses developed strychnine poisoning after ingesting strychnine contaminated barley (0.5%, 5,000 ppm) that was used as gopher bait. Manifestations of toxicity included stiff gait, muscle fasciculations, stumbling, tetanic seizures, and nystagmus. Treatment included activated charcoal, mineral oil laxative, sedation (diazepam, pentobarbital, xylazine and chloral hydrate) and furosemide. Two of the horses died. Of the survivors one developed aspiration pneumonia and facial paralysis which resolved over 28 days (Stoltenow et al, 2002).

11.1.13)

A) OTHER

1) Signs include spinal cord reflexes (tonic-clonic seizures, opisthotonus), dyspnea, cyanosis.

Treatment

11.2.1)

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

5) SMALL ANIMALS: Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only.
6) In the case of a poisoning involving large animals, consult a veterinary poison control center.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) EMESIS CONTRAINDICATED -

1) Emesis or lavage is NOT RECOMMENDED since these procedures may precipitate seizures. Activated charcoal should be administered immediately to minimize gastrointestinal absorption.

b) ACTIVATED CHARCOAL/CATHARTIC -

1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
3) ACTIVATED CHARCOAL/HORSES: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
4) ACTIVATED CHARCOAL/RUMINANTS: Administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
5) CATHARTICS/HORSES: Mineral oil is administered 30 minutes after activated charcoal. DOSE: 4 to 6 liters in adult horses and 1 to 4 liters in neonates or foals.

a) Magnesium sulfate: 0.2 to 0.9 grams/kilogram (500 grams for adults).
b) The sulfate laxatives are especially effective when given 30 to 45 minutes after mineral oil administration.
c) Carbachol (lentin): administer 1 milligram to an adult.

6) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.

a) The sulfate laxatives are especially effective when given 30 to 45 minutes after cathartic administration.
b) Mineral oil: Do not administer within 30 minutes of activated charcoal. DOSE: small ruminants and swine, 60 to 200 milliliters; cattle, 0.5 to 1 gallon.
c) Magnesium oxide: (Milk of Magnesia) Small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os.
d) Give these solutions via stomach tube and monitor for aspiration.

11.2.5)

A) GENERAL TREATMENT

1) Administer pentobarbital to maintain relaxation. 10% methocarbamol 150 mg/kg IV, repeat 1/2 dose if needed. OR, administer 5% glyceryl guiaiacolate 110 mg/kg IV. Repeat as necessary.

Range Of Toxicity

11.3.2)

A) The median lethal dose of strychnine is (Meiser & Hagedorn, 2002):

1) Rats - 3-8 mg/kg
2) Dogs - 0.76 mg/kg
3) Cats - 2.0 mg/kg
4) Pigs - <1 mg/kg
5) Cattle and horses - 0.5 mg/kg

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) EMESIS CONTRAINDICATED -

1) Emesis or lavage is NOT RECOMMENDED since these procedures may precipitate seizures. Activated charcoal should be administered immediately to minimize gastrointestinal absorption.

b) ACTIVATED CHARCOAL/CATHARTIC -

6) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.

Sources

References

General Bibliography

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STRYCHNINE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Reproductive

Carcinogenicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Other

Clinical Effects

Treatment

Range Of Toxicity

Continuing Care

Sources

General Bibliography